PilZ domain is part of the bacterial c-di-GMP binding protein


Sep 29, 2013 (4 years and 9 months ago)


Vol.22 no.1 2006,pages 3–6
Sequence analysis
PilZ domain is part of the bacterial c-di-GMP binding protein
Dorit Amikam
and Michael Y.Galperin
Department of Biotechnology and Environmental Sciences,Tel-Hai Academic College,Tel-Hai,Israel,
Institute of Oncology,Hadassah University Medical Center,Ein-Kerem,Jerusalem,Israel,and
National Center for
Biotechnology Information,National Library of Medicine,National Institutes of Health,Bethesda,MD 20894,USA
Received on October 17,2005;revised on October 20,2005;accepted on October 21,2005
Advance Access publication October 25,2005
Associate Editor:Alex Bateman
Recent studies identified c-di-GMP as a universal bacterial secondary
messenger regulating biofilm formation,motility,production of extra-
cellular polysaccharide and multicellular behavior in diverse bacteria.
However,except for cellulose synthase,no protein has been shown to
bind c-di-GMP and the targets for c-di-GMP action remain unknown.
Here we report identification of the PilZ (‘pills’) domain (Pfam domain
PF07238) in the sequences of bacterial cellulose synthases,alginate
biosynthesis protein Alg44,proteins of enterobacterial YcgRand firmi-
cute YpfA families,and other proteins encoded in bacterial genomes
and present evidence indicating that this domain is (part of) the long-
sought c-di-GMP-binding protein.Association of the PilZ domain with
a variety of other domains,including likely components of bacterial
multidrug secretion system,could provide clues to multiple functions
of the c-di-GMP in bacterial pathogenesis and cell development.
Supplementary information:http://www.ncbi.nlm.nih.gov/
The recent identification of bis-(3
)-cyclic dimeric guanosine
monophosphate,c-di-GMP,as a universal secondary messenger in
bacteria was a key advance in microbiology,made possible,in part,
by comparative genome analysis (Galperin et al.,2001;D’Argenio
and Miller,2004;Galperin,2004;Jenal,2004;Ro¨mling et al.,
2005).The GGDEF (formerly DUF1) and EAL (formerly DUF2)
domains,whose involvement in c-di-GMP turnover was discovered
in the groundbreaking work by Moshe Benziman and co-workers
(Tal et al.,1998),were found to be among the most abundant
domains encoded in bacterial genomes,suggesting that c-di-GMP-
dependent regulation was widespread in the bacterial world
(Galperin et al.,2001;Galperin,2005).Indeed,just in the past
two years,c-di-GMP was implicated in regulating transition
between motility and sessility in Escherichia coli and Salmonella
typhimurium,twitching motility in Pseudomonas aeruginosa,bio-
film formation in Vibrio cholerae and Yersinia pestis,and photo-
synthesis gene expression in Synechococcus elongatus (Huang
et al.,2003;Kirillina et al.,2004;Simm et al.,2004;Thomas
et al.,2004;Tischler and Camilli,2004).An important advance was
the recent demonstration that the diguanylate cyclase (c-di-GMP
synthetase) activity resides in the GGDEF domain (Paul et al.,
2004;Ryjenkov et al.,2005),whereas the EAL domain functions
as c-di-GMP-specific phosphodiesterase,hydrolyzing c-di-GMP to
linear diguanylate GpGp (Bobrov et al.,2005;Christen et al.,2005;
Schmidt et al.,2005).Still,mechanisms of c-di-GMP-dependent
signaling remain unknown,owing to the scarcity of data on the
targets of c-di-GMP action.
In the original study of the regulation of the cellulose synthase
in Acetobacter xylinum (currently Gluconacetobacter xylinus) and
other bacteria,Benziman and co-workers detected c-di-GMP bind-
ing to the cellulose synthase with most label bound to its b-subunit,
BcsB (Amikam and Benziman,1989;Mayer et al.,1991).These
data suggested that BcsB was the c-di-GMP binding protein,which
was reflected in its SwissProt annotation.Subsequent studies,how-
ever,revealed that c-di-GMP was actually binding to a 200 kD
membrane-bound protein complex (Weinhouse et al.,1997),
which has not been further characterized,but could correspond
to the dimer of the a-subunit or to the second form of cellulose
synthase whose single polypeptide chain contained both subunits
(Saxena and Brown,1995).Hence,it remained unclear which part
of cellulose synthase,if any,would bind c-di-GMP and what were
its other cellular targets.Our previous attempts to identify the c-di-
GMP-binding adaptor protein by computational means have been
unsuccessful,as no known protein exhibited the same phyletic
distribution as the GGDEF and EAL domains (Ro¨mling et al.,
2005).Here we report identification of the PilZ (‘pills’) domain
(Pfam domain PF07238,Bateman et al.,2004) in the sequence of
bacterial cellulose synthases and present evidence indicating that
this domain is the long-sought c-di-GMP-binding protein.
Development of twitching motility in P.aeruginosa is governed by
about 40 genes (Mattick,2002).Functions of most of them are
known or could be predicted based on the available experimental
data.PilZ,encoded by P.aeruginosa PA2960 gene,is a 118 amino
acid protein (Fig.1) that remains one of the very few without an
To whom correspondence should be addressed.
Published by Oxford University Press 2005
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